Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence

Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b)

Background: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. Results: Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.10421043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. Conclusions: The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed. © 2020 The Author(s)

Fast Linear State Estimation for Unbalanced Distribution Systems Using Hybrid Measurements

Distribution system state estimation (DSSE) is traditionally solved iteratively using unsynchronized measurements provided by the SCADA system and/or smart meters. This article puts forward a decoupled linear state estimation (SE) method for unbalanced distribution systems. Contrary to conventional methods, the proposed linear DSSE (LDSSE) method can function with purely unsynchronized or hybrid synchronized/unsynchronized measurements. In the case of purely unsynchronized measurements, the voltage phase angles of the reference bus are acquired through local measurements. In the first stage, the proposed LDSSE method estimates the voltage phase angles in terms of network parameters and available measurements. These are referred to as pseudo-synchronized voltage phase angles, which establish a basis for deriving pseudo-synchronized voltage/current phasors. In the second stage, a set of linear equations are derived for each phase separately. Solving these equations results in estimates for voltage phasors. The linearity and decoupled nature of the proposed LDSSE method significantly reduces the computation time without impacting the accuracy of estimates. The superiority of the proposed LDSSE method over the existing methods is verified using extensive simulations conducted on several test feeders, delivering results 20 times faster than the nonlinear DSSE (NDSSE) on the 8500-bus test feeder

Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7) diagnosed genetically. © 2018 John Wiley & Sons Ltd

Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi�Bickel Syndrome

Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG�s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG�s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. © Copyright © 2021 Eghbali, Fatemi, Salehpour, Abiri, Saei, Talebi, Olyaei, Yassaee and Modarressi

Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; Reporting novel and recurrent mutations

Background: Glanzmann thrombasthenia (GT) is a rare autosomal recessive abnormality of platelet aggregation with quantitative and/or qualitative abnormality of αIIbβ3 integrin. The αIIbβ3 is a platelet fibrinogen receptor, which is required for platelet aggregation, firm adhesion, and also spreading. The disease is more prevalent in the populations with a higher rate of consanguineous marriages as in some Middle Eastern populations including Iraq, Jordan, and Iran. Different types of mutations in ITGA2B and ITGB3 genes have been previously reported to cause the disease. Result: In this study, 16 patients with the clinical diagnosis of GT were studied. Direct sequencing of the exons and exon-intron boundaries of the above genes revealed mutations in 14 patients (detection rate: 87.5). Briefly, out of fifteen types of identified mutations, 14 were novel. Seven mutations in the ITGB3 gene included 4 missense c.2T > C, c.155 G > T, c. 538 G > A, c.1990 G > T, one nonsense mutation c.1303 G > T, a small deletion c.1656-1658delCTC and a deletion of one nucleotide c.401delA. Mutations in the ITGA2B were 8 different mutations consisting 2 missense c.286 T > A, c.842 C > T, 2 deletions c.1899 del T, c.189-319-236del, an insertion c.1071-1072insG and one splice site mutations c.409-3 C > G, one synonymous mutation that might alter the normal splicing process c.1392 A > G and a nonsense mutation c.1555 C > T. The causative mutation in 2 patients remained unknown. Using long-range PCR and sequencing, we found a rather large deletion. The break point of this deletion covers 319 nt from the last part of the first intron and 48 nt from the beginning of the second exon of ITGA2B gene. The deletion was also detected in two unrelated patients with the same ethnicity. In addition, in silico analyses of novel mutations were performed. Conclusion: There was no recurrent mutation in the studied population. This may be due to either small sample size or the heterogeneity of the studied population. © 2019 The Author(s)

Comparing the effectiveness of vitamin D plus iron vs vitamin D on depression scores in anemic females: Randomized triple-masked trial

Background: Low levels of 25-hydroxyvitamin D (25(OH)D) have been related to depression and anxiety. It seems that anemia is associated with vitamin D deficiency. We aimed to evaluate the effects of iron-vitamin D co-supplementation versus vitamin D alone on depression scores in anemic females with low levels of serum 25-hydroxyvitamin D. Methods: This randomized controlled trial was conducted on eighty premenopausal females who were recruited between May 2015 and October 2015 from primary health care centers. Women with anemia and low concentrations of 25(OH)D were randomized to either 1000 IU/d vitamin D plus 27 mg/d iron (D-Fe) or vitamin D plus placebo supplements (D-P) for 12 weeks. Depressive and anxious symptoms were evaluated with the Beck Depression Inventory (BDI) with subscales 1-13 and 14-21 and Beck Anxiety Inventory (BAI). To compare the groups, Mann-Whitney or chi-squared tests were used and within groups comparison was performed using Wilcoxon signed ranks test. The study was registered on www.clinicaltrial.org as NC 01876563. Results: The serum concentrations of 25(OH)D were increased significantly in both groups at the end of the study. In both groups, there was a significant improvement in total BDI, the BDI subscale, and the BAI scores (p0.05). Conclusion: Although the potential positive effect of vitamin D on mental health was evident, iron plus vitamin D co-supplementation did not demonstrate any significant benefits over vitamin D alone, neither in depression score reduction nor anxiety symptoms